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標題: | 探討人格特質、遺傳因子及保護因子對自殺行為之影響 Investigation of the effects of personality, genetic variants and protective factors for suicidal behaviors |
作者: | Mei-Hsin Su 蘇美心 |
指導教授: | 郭柏秀 |
關鍵字: | 自殺,全基因掃描研究,人格,情感性疾患,神精質人格, suicide,genome-wide association study,personality,mood disorder,neuroticism, |
出版年 : | 2020 |
學位: | 博士 |
摘要: | 自殺是一項重要的公共衛生議題,同時也是台灣主要死因排名的第 11 位。自殺的成因相當複雜,包含了生理、心理、病理、及環境等因素的交互作用。在眾多複雜的成因中,心理因素之一的人格特質在過去研究中被發現:即使個案經歷到相同的環境或病理因素,但自殺的風險卻會因人格特質的不同而有顯著的差異。說明了人格在自殺議題中扮演著修飾因子的角色。除此之外,遺傳
及分子精神病學相關的研究紛紛發現某些遺傳因子與人類行為的失調(包括自殺)相關。因此本研究第一即是探討人格特質與自殺意念與自殺企圖的相關性、第二是以全基因掃描的方式找出與自殺企圖相關的遺傳因子,並且計算人格的多基因風險分數,探討人格的基因分數與自殺企圖的相關性。第三是計算自殺的多基因風險分數,並利用此分數找出帶有較多自殺相關遺傳因子之極度高風險個案,進一步在極度高風險個案中尋找可能的保護因子。本研究結果發現,在人格分數中,神精質及傷害畏避分數較高者會有較高的風險出現自殺意念及自殺企圖,且人格對於自殺的影響與是否患有精神疾患是獨立的。另外,研究結果也發現神精質人格分數可以將企圖自殺者從儘具有意念的個案中分別出來。至於全基因掃描及多基因風險評分的研究結果則發現,在情感性疾患的病人中,rs7708072 之位點(位於 NNT-AS1 基因之上) 與自殺企圖有顯著相關且也自殺企圖的盛行率會隨著神精質及盡責性這兩項人格的基因風險分數的提高而增加。在保護因子的分析中則發現,男性、發病年齡愈晚的情感性疾患、以及家庭支持等因素在極高風險的個案中會是自殺的保護因子。建議未來可將神精質人格及自殺之多基因風險分數合併考慮,用以作為鑑別自殺高風險個案之指標。 Suicide ideation (SI) and suicide attempt (SA) are important public health issues worldwide and suicide is the 11th leading cause of death in Taiwan. Among the complex contributions to suicide, personality is a moderater when subjects experience the same psychopathological or environmental factors. In addition, SA-related markers have been widely reported in genetic and molecular psychiatry studies. Hence the first aim of this study is to investigate the effect of single and combination traits of personality (neuroticism (N), extraversion (E), harm avoidance (HA), and novelty seeking (NS) were included) on SI and SA. Second, we conducted a genome-wide association study (GWAS) for SA in mood disorder patients to identify SA-related markers. Also, we calculated the polygenic risk score (PRS) of personality (E, N, conscientiousness (C) and openness (O) were included) and then examine the association between personality PRS and SA. Finally, we used PRS of SA (PRSsa) to identify subjects who carried more SA-related genetic markers and detect possible protective factors. In the results, we found higher N or HA are associated with increased risk of SI and SA, and the effect of personality traits is independent of mood disorder diagnosis. We also found higher N score further distinguishes attempters from ideators among mood disorder patients. For GWAS analysis, rs7708072 in NNT-AS1 gene met genomewide significance in mood disorder patients and an upward trend of SA prevalence was associated with increasing PRS of N and C. Male gender, later onset age of mood disorder and family support are protective factors of SA in the top 20% of PRSsa group. Target on identifying a high risk group to investigate further the mechanisms underlying the link between resilience factors and suicidal behaviors for suicide prevention will be valuable for future study. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65038 |
DOI: | 10.6342/NTU202000543 |
全文授權: | 有償授權 |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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